The long-term research goal is to improve understanding of the relationship of plasma androgen levels to androgen action. We conceptualize androgen actions as dependent upon the total effect of the free (unbound) plasma concentrations of the 17 beta-hydroxysteroids, testosterone, dihydrotestosterone, androstenediol, and androstanediols. Androgen disposition, end-organ reaction, and androgen antagonists then determine the response. We propose to quantitate these factors so as to test these concepts. The specific aims of the proposed research are to a) develop improved methods for the assay of plasma androgens, b) study the control of plasma androgen levels, c) determine the relation of testosterone estradiol binding globulin (TEBG)-binding of androgens to 0ndrogen disposition, including the excretion of urinary free testosterone, d) determine the effect of obesity on androgen disposition, e) determine the extent to which 17 beta-hydroxysteroids and 17-ketosteroids act in target organs independently of their conversion to plasma testosterone, f) study female hirsutism as a model hyperandrogenic state, and g) measure the free plasma estradiol and determine the degree to which it is influenced by competition with androgenic 17 beta-hydroxysteroids for binding sites on TEBG. Plasma steroids will be measured using highly specific antisera. These antisera will be raised against steroids conjugated to proteins through the B or C rings and/or adsorbed with cross-reacting steroids. The relationship between serum testosterone and LH will be studied in hypogonadal rats. Adrenal androgen secretion will be studied in monolayer culture. The metabolic clearance rate and urinary excretion of various C19 steroids will be studied with respect to TEBG levels and obesity. Plasma binding of steroids will be measured by dialysis, adsorption, and/or gel filtration techniques. Androgenic potency of steroids will be evaluated in vitro in rat ventral prostate. BIBLIOGRAPHIC REFERENCE: Bibbo, M., Gill, W. B., Azizi, F., Blough, R., Fang, V.S., Rosenfield, R. L., Schumacher, G. F. B., Sleeper, K., Sonek, M. G., Wied, F., and Wied, G.: Follow-up study of male and female offspring of DES-exposed mothers. Obstet. & Gynecol. 49:1-8, 1977.